Lab talk

Aug 7, 2014

Understanding autophagy for enhanced carcinoma therapy

Poly(amidoamine) (PAMAM) dendrimers are promising nanomaterials for drug delivery. They have a unique tree-like structure, monodispersity and tunable properties. Reporting in Nanotechnology, researchers at Fudan University in China explore the role and mechanism of autophagy induced by PAMAM dendrimers in hepatocellular carcinoma cells. This provides new insights into the effect of autophagy on drug delivery nanomaterials and tumor cells. It also contributes to the use of PAMAM dendrimer-based hepatocellular carcinoma therapy.

Autophagy is a phenomenon in which eukaryotes degrade long-lived proteins and damaged organelles such as mitochondria. Activated during cell starvation and other stresses, it is involved in several human pathologies such as cancer and aging. It plays the role of a double-edged sword as it can either promote cell survival or initiate type II programmed cell death. This report is the first to show that autophagy inhibition may lead to the enhancement of PAMAM dendrimer-based hepatocellular carcinoma therapy.

Autophagy suppression

The authors demonstrate that PAMAM dendrimers induce the accumulation of autophagic vacuoles in hepatocellular carcinoma cells. To explore the role and mechanism of autophagy induced by PAMAM dendrimers, autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) are used to suppress it. Cells treated with autophagy inhibitors combined with PAMAM dendrimers show significantly enhanced growth inhibition and apoptotic effects in hepatocellular carcinoma cells.

ROS effects

Reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC) is applied to investigate the the role of oxidative stress in PAMAM dendrimer-treated hepatocellular carcinoma cells. It is found that the presence of NAC enhances the growth inhibition and apoptotic effects induced by the PAMAM treatment. It also significantly reduces the autophagic effects.

Besides the activation of inflammasomes, the suppression of the Akt/mTOR signaling pathway and the activation of the Erk 1/2 signaling pathway are also involved in the autophagy induced by PAMAM dendrimers in hepatocellular carcinoma cells.

About the author

Yubin Li is a PhD candidate at Fudan University in the Department of Biosynthesis and the Key Laboratory of Smart Drug Delivery supervised by Dianwen Ju. Ju’s group carries out a variety of research investigating the role and mechanism of autophagy induced by biomedical nanomaterials.